Myocardial infarction is a common presentation of ischemic heart disease/coronary artery disease. The World Health Organization estimated in 2004 that 12.2% of worldwide deaths occurred as a result of ischemic heart disease. Ischemic heart disease was also deemed the leading cause of death in middle to high income countries and second only to respiratory infections in lower income countries. The Global Burden of Disease: World Health Organization 2004 Update, Geneva (2008). Worldwide more than 3 million people present with a ST elevation myocardial infarction (STEMI) and 4 million people present with a non-ST elevation myocardial infarction (NSTEMI) a year. White, et al., Acute Myocardial Infarction, Lancet 372 (9638), pp. 570-84 (August 2008).
Rates of death from ischemic heart disease have slowed or declined in most high income countries, although cardiovascular disease still accounted for 1 in 3 of all deaths in the USA in 2008. Roger, et al., Executive summary: Heart Disease and Stroke Statistics—2012 update: A report from the American Heart Association, Circulation 125 (1), pp. 188-97 (January 2012).
In contrast, ischemic heart disease is becoming a more common cause of death in the developing world. For example in India, ischemic heart disease had become the leading cause of death by 2004; accounting for 1.46 million deaths (14% of total deaths). Deaths in India due to ischemic heart disease were also expected to double during 1985-2015. Gupta, et al., Epidemiology and Causation of Coronary Heart Disease and Stroke in India, Heart 94 (1), pp. 16-26 (January 2008).
Globally, it is predicted that disability adjusted life years (DALYs) lost to ischemic heart disease will account for 5.5% of total DALYs in 2030, making it the second most important cause of disability (after unipolar depressive disorder), as well as the leading cause of death by this date.
A myocardial infarction (a common presentation of ischemic heart disease) often occurs when a coronary artery becomes occluded and can no longer supply blood to the myocardial tissue, thereby resulting in myocardial cell death. When a myocardial infarction occurs, the myocardial tissue that is no longer receiving adequate blood flow ultimately dies (without effective intervention) and is eventually replaced by scar tissue.
Within seconds of a myocardial infarction, the under-perfused myocardial cells no longer contract, leading to abnormal wall motion, high wall stresses within and surrounding the infarct, and depressed ventricular function. The high stresses at the junction between the infarcted tissue and the normal tissue lead to expansion of the infarcted area and remodeling, i.e. a cascading sequence of myocellular events, over time.
Various methods for treating a myocardial infarction are often employed. Such methods include stabilizing the hemodynamics associated with a myocardial infarction via systemic delivery of various pharmacological agents and restoring the patency of occluded vessels via thrombolytic therapy or angioplasty and stents.
Several additional methods for treating a myocardial infarction are directed to re-establishing blood flow to the ischemic area through stimulation of angiogenesis. Re-establishing blood flow at the ischemic area can, and in many instances will, reduce symptoms associated with a myocardial infarction and/or improve cardiac function.
Some methods for re-establishing blood flow and rehabilitating the heart involve invasive surgery, such as bypass surgery or angioplasty. Other methods employ lasers to bore holes through the infarctions and ischemic area(s) to promote blood flow. As one can readily appreciate, there are numerous incumbent risks associated with the noted methods.
A further method for treating a myocardial infarction is the direct or selective delivery of bioactive or pharmacological agents to the infarction and/or ischemic area (i.e. effected or damaged cardiovascular tissue). Direct delivery of a bioactive or pharmacological agent to the effected cardiovascular tissue is often preferred over the systemic delivery for several reasons. A primary reason is that a substantially greater concentration of such agents that can be delivered directly into the effected cardiovascular tissue, compared with the dilute concentrations possible through systemic delivery. Another reason is the risk of systemic toxicity which can, and in many instances will, occur with doses of pharmacological agents that are typically required to achieve desired drug concentrations in the effected cardiovascular tissue.
One common method of delivering bioactive or pharmacological agents to effected cardiovascular tissue, e.g. damaged myocardial tissue, comprises advancing a catheter through the vasculature and into the heart to inject the agents directly into the effected cardiovascular tissue from within the heart.
Another method of delivering bioactive or pharmacological agents to effected cardiovascular tissue comprises epicardial, direct injection into the tissue during an open chest procedure. The bioactive agents that can be, and have been, administered to the effected cardiovascular tissue include various pharmacological agents, such as antithrombotic agents, e.g., heparin, hirudin, and ticlopidine, and cells that are capable of maturing into actively contracting cardiac muscle cells or regenerating cardiovascular tissue. Examples of such cells include myocytes, myoblasts, mesenchymal stem cells, and pluripotent cells.
However, to date, cell therapy of effected cardiovascular tissue has not reached its full potential, due, in part, to the failure of implanted cells to survive and regenerate the damaged tissue in ischemic area(s) or regions with inadequate vascularization.
It would thus be desirable to provide bioactive and pharmacological agents (and compositions) that promote tissue survival and induce neovascularization and regeneration of effected or damaged cardiovascular tissue, and improved methods for delivering same to effected cardiovascular tissue.
It is therefore an object of the present invention to provide bioactive and pharmacological agents (and compositions) that promote tissue survival, and induce neovascularization and regeneration of damaged cardiovascular tissue.
It is another object of the present invention to provide extracellular matrix (ECM) compositions, which, when delivered to damaged biological tissue; particularly, cardiovascular tissue, induce neovascularization, host tissue proliferation, bioremodeling, and regeneration of cardiovascular tissue and associated structures with site-specific structural and functional properties.
It is yet another object of the present invention to provide improved methods and systems for administering an ECM composition directly to damaged or diseased biological tissue; particularly, cardiovascular tissue.